Monoclonal Antibody Therapy With Sargramostim and Interleukin-2 in Treating Children With Neuroblastoma
Study Details
Study Description
Brief Summary
Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood. Interleukin-2 may stimulate a person's white blood cells to kill cancer cells. Combining monoclonal antibody therapy with sargramostim or interleukin-2 may kill more tumor cells. Phase I trial to study the effectiveness of monoclonal antibody therapy given with sargramostim and interleukin-2 in treating children with neuroblastoma who have just completed bone marrow or peripheral stem cell transplantation
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
PRIMARY OBJECTIVES:
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Determine the maximum tolerated dose of monoclonal antibody (MOAB) ch14.18 when combined with sargramostim (GM-CSF) and interleukin-2 (IL-2) after autologous bone marrow or peripheral blood stem cell rescue in children with neuroblastoma.
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Determine the toxic effects of this regimen in these patients. III. Determine the pharmacokinetics, including antibody level, antibody-binding activity, and presence of human anti-chimeric antibodies, of this regimen in these patients.
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Determine the activity of IL-2 and MOAB ch14.18 against tumor cells in terms of response using standard clinical measurements such as bone marrow immunocytology in these patients.
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Determine the extent of coating of tumor cells (bone marrow metastases) by MOAB ch14.18 in these patients.
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Determine the feasibility of isotretinoin administered between courses beginning after course 2 in these patients.
OUTLINE: This is a multicenter, dose-escalation study of monoclonal antibody (MOAB).
Patients receive MOAB IV over 5 hours on days 7-10 during courses 2 and 4 and on days 3-6 during courses 1, 3, and 5; sargramostim (GM-CSF) IV over 2 hours or subcutaneously daily on days 0-13 during courses 1, 3, and 5; interleukin-2 IV continuously on days 0-3 and 7-10 during courses 2 and 4; and oral isotretinoin twice daily on days 14-27 during courses 2 and 4 and on days 10-23 during courses 3 and 5. Treatment repeats every 24-32 days for 5 courses in the absence of unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of MOAB until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A minimum of 6 additional patients are treated at the MTD.
Patients are followed every other week for 2 months and then every 3 months for 6 months.
PROJECTED ACCRUAL: Approximately 6-16 patients will be accrued for this study within 1 year.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment (monoclonal antibody Ch14.18, aldesleukin) Patients receive MOAB IV over 5 hours on days 7-10 during courses 2 and 4 and on days 3-6 during courses 1, 3, and 5; sargramostim (GM-CSF) IV over 2 hours or subcutaneously daily on days 0-13 during courses 1, 3, and 5; interleukin-2 IV continuously on days 0-3 and 7-10 during courses 2 and 4; and oral isotretinoin twice daily on days 14-27 during courses 2 and 4 and on days 10-23 during courses 3 and 5. Treatment repeats every 24-32 days for 5 courses in the absence of unacceptable toxicity. |
Biological: monoclonal antibody Ch14.18
Given IV
Other Names:
Drug: isotretinoin
Given orally
Other Names:
Biological: aldesleukin
Given IV
Other Names:
Biological: sargramostim
Given IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Maximum tolerated dose of monoclonal antibody (MOAB) ch14.18 when combined with sargramostim and IL-2 after autologous bone marrow or peripheral blood stem cell rescue in children with neuroblastoma [32 days]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Must have recently completed a course of myeloablative therapy followed by autologous stem cell (bone marrow or peripheral blood) rescue (ASCT)
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Patients must have a diagnosis of neuroblastoma based upon tumor histology or bone marrow metastases and elevated urine catecholamine metabolites; greater than 98% of neuroblastomas are GD2-positive without intratumor heterogeneity, so these tumors will not be immunostained prior to study entry
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Patients entered on CCG-3951 may become eligible following the third course of high-dose chemotherapy followed by peripheral blood stem cell (PBSC) rescue; patients treated on institutional (local) protocols of high-dose chemotherapy with PBSC rescue may also become eligible after one or more courses of PBSC rescue
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Patients must enter onto study within 8 weeks after the total absolute phagocyte count [neutrophils (segs + bands) + monocytes] is > 1,000/uL; the APC criteria include counts obtained while on G-CSF therapy
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Patients must have a performance status of 0, 1 or 2 and patients must have a life expectancy of >= 2 months
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Serum creatinine =< 1.5 x normal, or creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 60 ml/min/1.73 m^2
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Total bilirubin =< 1.5 x normal
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Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 5 x normal
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Veno-occlusive disease, if present, should be stable or improving
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Shortening fraction of >= 27% by echocardiogram, or ejection fraction of > 50% by gated radionuclide study
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Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) > 60% of predicted by pulmonary function test
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For children who are unable to do pulmonary function tests (PFTs), no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% on room air
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Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
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Central nervous system (CNS) toxicity < grade 2
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Patients must have a double lumen catheter or single lumen and peripheral IV so that interleukin (IL)-2 and ch14.18 can be given separately
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Patients who remain evaluable for response on Phase II/III studies (i.e. CCG-3891) are not eligible for this study; however, patients treated on Phase I studies (i.e. CCG-3951) and patients who are no longer evaluable on Phase II/III studies (i.e. progressive disease following therapy) will be eligible
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Patients who were previously treated with antibody 14.G2a or ch14.18 are ineligible for this study
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Patients requiring chronic use of corticosteroids are ineligible
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Corticosteroid, immunosuppressive drugs, myelosuppressive chemotherapy, and retinoic acid must not be given within 14 days prior to study entry
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Radiation therapy must not be given within seven days prior to study entry or during therapy
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All patients and/or their parents or legal guardians must sign a written informed consent
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All institutional, FDA, and NCI requirements for human studies must be met
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Oncology Group | Arcadia | California | United States | 91006-3776 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Andrew Gilman, Children's Oncology Group
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCI-2012-01527
- 0935
- CDR0000063533